Section 1 of Part 2: How Could A Gluten Intolerance Cause Amyotrophic Lateral Sclerosis (ALS) Or Lou Gehrig’s Disease?

This is part 2 of a 5 part series discussing how ALS could be caused by a gluten intolerance, other types of allergies, and/or by a reaction to lectins. In this part of the series, the possible association between ALS and a gluten intolerance is discussed. Due to the length of this part, I will need to break it into 8 posts/sections. At the end of this post, I have outlined the series for you. Today, section one will discuss how reactions against transglutaminases may contribute to symptoms.

Section 1: How Could Antibody Reactions Against Transglutaminases Contribute To ALS

Transglutaminases are very important enzymes. These enzymes are involved in many functions, such as tissue repair, signalling processes, cellular differentiation (cells become more specialized), matrix stabilization (tissue that provides support to cells), and apoptosis (biochemical change that causes death in cells that are not needed). Without it, tissue repair is hindered, unfavourable cellular changes can occur, abnormal cells could grow uncontrollably leading to cancer and signalling between cells (including nerve cells) could be negatively affected. These changes could occur in any area of the body where the enzyme is not available.

You may be wondering why I’m so interested in transglutaminases and what does this have to do with ALS. Well, with a gluten intolerance, antibody attacks against tissue transglutaminase can cause many problems. Since I have celiac disease and have experienced the result of this reaction, I am intrigued by this enzyme. With celiac disease (CD), tissue transglutaminase 2 is damaged by antibodies in the bowel, antibodies against tissue transglutaminase 3 occur in dermatitis herpetiformis (another form of gluten intolerance) and antibodies attack tissue transglutaminase 6 in gluten ataxia (form of gluten intolerance causing neurological disease). Since many neurological symptoms can occur with gluten intolerance (due to immune reactions against transglutaminase and nerve tissue), it seems reasonable to suspect that cross reactions to transglutaminases could occur in patients with ALS.

Like celiac disease, dermatitis herpetiformis and gluten ataxia, perhaps, immune responses to gluten and transglutaminase in the gut leads to autoimmune activity against various forms of transglutaminases throughout the body (in this case, the central and peripheral nervous system). This could result in different types of neurological diseases, such as ALS. IgA and IgG antibodies against transglutaminase (and nerve tissue) could lead to inflammation and autoimmune damage in the central and peripheral nervous system. This type of damage could interrupt the neuronal impulses and lead to the neurodegenerative disease process seen in ALS. I believe this type of reaction is very likely to occur considering that neuronal impulses can be negatively affected with a gluten intolerance.

In studies, researchers found that transglutaminase levels were higher in the initial stages of ALS. However, as the ALS progressed, abnormally low levels of transglutaminase was found in the cerebral spinal fluid of patients with clinical motor dysfunction. In autopsies (from 5 patients with ALS), tissue (transverse sections) taken from the human spinal cord (lumbar and thoracic) showed very low transglutaminase activity (in the ventral, dorsal, and lateral regions). The researchers theorize that the transglutaminase enzyme is low because the supply is exhausted due to the demand for tissue repair with ALS. The researchers in another study suggested that the enzyme may leak out of the spinal cord into the CSF and then into the bloodstream leaving low levels in the CSF and spinal cord [1,2].

I think that it is reasonable to suspect that IgA and IgG antibodies may initially react to gluten, then cross react against tissue transglutaminase in the central and peripheral nervous system of patients with ALS. Tissue transglutaminase has an affinity for undigested gluten so a cross reaction could easily occur. The reaction to gluten could initially increase levels, then as the antibodies identify and attack transglutaminase, levels would be depleted (like in the studies). Cross reactions against neuronal tissue could also occur, just as it does against endomysial tissue in celiac disease and brain plus nerve tissue in gluten ataxia. This autoimmune reaction could be the culprit underlying the damage found in the brain and spinal cord of patients with ALS.

Unfortunately, this damage would increase the demand for tissue transglutaminase (for tissue repair) and this would deplete the supply further (may help explain the low levels in the studies). This type of reaction occurs with gluten ataxia (a neurological condition that results from antibody reactions to gluten and transglutaminase). It isn’t a far stretch to suspect that immune reactions to gluten and cross reactions against tissue transglutaminase could be the underlying culprit in ALS.

I believe researchers need to conduct further research to look at the role and types of transglutaminases that are present in the the brain, spinal cord (and CSF), how the transglutaminases are affected with ALS, and how the ingestion of gluten may be promoting a cross reaction against tissue transglutaminase and nerve/brain tissue in this illness. If a gluten intolerance is responsible, a gluten-free diet may take a year or longer to work, but is a nice alternative to the current prognosis associated with ALS.

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The rest of Part 2, along with parts, 3, 4, and 5 will follow in the next 2-3 months.

Shelly,
Great article, thanks so much. I am a 61 year old male that has suffered from seizure activity since I was 12. Two year ago I lost about 60 pounds and noticed that my seizure activity decreased while I was using the Medifast foods to loose weight. The short version is that I had DNA testing done and found markers that indicated gluten intolerance. After a 6 month purge I am seizure free as long as I stay away from gluten. I use a supplement called GlutenFlam (K-52) whenever I suspect I may have ingested gluten. I have never had a celiac problem.
I just recently had a friend diagnosed with ALS and found your site while doing some research. I will sign up for your newsletter. Thanks so much for work, I look forward to sharing this information with my friend.
Sincerely,
Greg

John L on
June 15th, 2011 11:11 am

I like the way your hypothesis is developing. I think a lot of the odd reactions to gluten may be caused by the damage done the small intestine and the resultant problems with nutrient absorption. Specifically vitamin D and magnesium. Both nutrients are sometimes mentioned in natural treatments for ALS and MS. I hope more research is done on this nutrient absorption issue.

I am also curious has anyone looked at Mr. Gehrig’s family history? I know he was first generation Norwegian. It would be interesting to know if there was a family history with gluten.

Thank you for this. My BIL has been suffering increasing ataxia, tremors, and spasticity; neurologists have been clueless. I just read Wheat Belly by Dr. William Davis, and realized he sounds like a very possible case of gluten-caused cerebellar ataxia. Then I remembered that his mother died of ALS, and started googling. Very good to find this.

Thank you for your comment. It is great that you are considering gluten intolerance as one contributing factor since there could be an association.

With regards to Lewy Body Dementia, I haven’t seen any research, but would not be surprised if there was a connection.

You may find my other post about Alzheimers interesting and also the neurology chapter in my book, “Gluten Toxicity”. Both discuss how immune reactions to gluten (and immune reactions to other foods) can affect the brain and the neurological system.

Cherie Litton on
January 17th, 2012 11:03 am

I have trigeminal neuralgia and my daughter, found out I need to be on an gluten-free diet. I have had allergies all my life, since a child. I have used different allergiest. I also have a vitamin D deficiency for years. Cherie Litton

Jay Henschen on
May 30th, 2015 2:51 pm

Shelly, I am looking forward to more of your info and also these posts from your followers of your articles. Six years ago I was on a bus trip. One of the lady travelers got to talking about how she had cured herself of MS. She said she went on a strict gluten-free diet and in a couple years she was declared free of MS. ALS and MS have some similarities in that the myelin sheath of nerves are affected. A neurologist might have arguments about that, but that is how I see it. My brother was recently diagnosed with ALS so I am very interested in following these articles & blogs.
Jay